RIN3

protein-coding

Ras and Rab interactor 3, the group of VPS9 domain containing

Gene summary

Summary: This protein encoded by this gene is a member of the RIN family of Ras interaction-interference proteins, which are binding partners to the RAB5 small GTPases. The protein functions as a guanine nucleotide exchange for RAB5B and RAB31. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Feb 2016]

MANE transcript

NM_024832.5

Inheritance

—

ClinVar variants

U:163B:13

Top phenotype

Lung adenocarcinoma

gnomAD constraint

pLI —, LoF o/e 0.62

Max pathogenic AF

—

Genomic locus

chr14:92,513,781-92,688,994

External References & Databases

Ensembl (ENSG00000100599)

Transcript & Mutation Effects

hg38 • Region Span ~175.2 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to RIN3 variants in ClinVar

4 Conditions Cataloged

not specifiedTotal: 162

not providedTotal: 6

Lung adenocarcinomaTotal: 4

RIN3-related disorderTotal: 3

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_024832.5. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous					1 clinvar	1
missense			158 clinvar	12 clinvar		170
nonsense			1 clinvar			1
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			4 clinvar			4
Total	0	0	163	12	1	176

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 16 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_024832.5	RefSeq	NP_079108.3	10	MANE Select
ENST00000216487.12	Ensembl	ENSP00000216487.7	10	MANE Select
NM_001319987.2	RefSeq	NP_001306916.1	9	Standard
ENST00000555589.5	Ensembl	ENSP00000450682.1	5	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Vesicle-mediated transport
Membrane Trafficking
Rab regulation of trafficking
RAB GEFs exchange GTP for GDP on RABs

Biological Process

endocytosis
signal transduction
positive regulation of GTPase activity

Molecular Function

GTPase activator activity
protein binding
Rab guanyl-nucleotide exchange factor activity
Rab GTPase binding

Cellular Component

early endosome
cytosol
cytoplasmic vesicle

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000216487
Coding exons: 10
Length: 175222
Individuals with no LoFs: 125678
Homozygous LoFs: 0
Heterozygous LoFs: 70
Defined: 125748
p: 0.000278

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.775	555	609	0.912	0.0000381	6324
Missense (PolyPhen)		165	192.11	0.85887		2003
Synonymous	-0.911	292	273	1.07	0.0000186	2079
Loss of Function	2.00	20	32.2	0.621	0.00000144	390

Population LoF Frequency

Population	CAF	p-value	Status
African	0.000072	0.000062	rare
Latino/Admixed American	0.00033	0.00032	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.00028	0.00022	rare
Finnish	0.0011	0.00083	notable
European (Non-Finnish)	0.00031	0.00030	rare
South Asian	0.000033	0.000033	rare
Other	0.00016	0.00016	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Ras effector protein that functions as a guanine nucleotide exchange (GEF) for RAB5B and RAB31, by exchanging bound GDP for free GTP. Required for normal RAB31 function. {ECO:0000269|PubMed:12972505, ECO:0000269|PubMed:21586568}.;

Recessive Scores

pRec: 0.0954

Intolerance Scores

LoFtool: 0.446
RVIS EVS: 0.17
RVIS percentile EVS: 64.99

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.960

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	High	Medium	High
Primary Immunodeficiency	High	High	High
Cancer	High	High	High